Mp03-01 Clinical, Pathologic and Genomic Profiles of Exceptional Responders to Anti-pd1 Therapy in Renal Cell Carcinoma
Year: 2016
Type: article
Abstract: You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I1 Apr 2016MP03-01 CLINICAL, PATHOLOGIC AND GENOMIC PROFILES OF EXCEPTIONAL RESPONDERS TO ANTI-PD1 THERAPY IN RENAL CELL CARCINOMA Mark Ball, Michael Johnson, Michael Gorin, Maria Rodriguez, Ming Zhang, Nick Papadopoulos, Michael Haffner, Hans Hammers, Luigi Marchionni, George Netto, Charles Drake, and Mohamad Allaf Mark BallMark Ball More articles by this author , Michael JohnsonMichael Johnson More articles by this author , Michael GorinMichael Gorin More articles by this author , Maria RodriguezMaria Rodriguez More articles by this author , Ming ZhangMing Zhang More articles by this author , Nick PapadopoulosNick Papadopoulos More articles by this author , Michael HaffnerMichael Haffner More articles by this author , Hans HammersHans Hammers More articles by this author , Luigi MarchionniLuigi Marchionni More articles by this author , George NettoGeorge Netto More articles by this author , Charles DrakeCharles Drake More articles by this author , and Mohamad AllafMohamad Allaf More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1894AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have correlated response to PD-1 blockade with PD-L1 over-expression, as well as cell-mediated immune transcripts. However, factors associated with long-term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy - exceptional responders who had durable, complete response and patients who had primary refractory disease. METHODS Patients with complete-response (CR) by RECIST or a near-complete response (defined as a PET complete response and 10% or less stable residual disease) at 24 months ″Exceptional responders″ (n=4) and patients with signs of progression on first imaging, ″primary refractory″ (n=3) were analyzed. Immunohistochemical staining for tumor PD-1L1 expression, and CD8 lymphocytes, whole-exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. RESULTS Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predicted mutation associated neoantigens than primary refractory patients (44 vs 8). Exceptional responders had a higher proportion of mutated chromatin remodeling genes than primary refractory patients. Expression analysis demonstrated acute phase and immune tolerance signatures in primary refractory patients, while exceptional responders had higher expression of T cell and innate immune signatures. PDL1 expression did not correlate with response. CONCLUSIONS Exceptional responders and primary refectory patients have distinct pathologic, genomic and RNA expression profiles. Larger studies are needed to fully elucidate the basis of response to PD-1 blockade in patients with renal cell carcinoma. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e19 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Mark Ball More articles by this author Michael Johnson More articles by this author Michael Gorin More articles by this author Maria Rodriguez More articles by this author Ming Zhang More articles by this author Nick Papadopoulos More articles by this author Michael Haffner More articles by this author Hans Hammers More articles by this author Luigi Marchionni More articles by this author George Netto More articles by this author Charles Drake More articles by this author Mohamad Allaf More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2333076513